ABCMdb

PMID: 21642448

Caldwell RA, Grove DE, Houck SA, Cyr DM
Increased folding and channel activity of a rare cystic fibrosis mutant with CFTR modulators.
Am J Physiol Lung Cell Mol Physiol. 2011 Sep;301(3):L346-52. Epub 2011 Jun 3., [PubMed]

Sentences

No. Mutations Sentence Comment

35 ABCC7 p.Val232Asp The folding defect caused by the V232D mutation appears to be due to the introduction of a charged residue into a region of CFTR that is embedded in the lipid bilayer of the ER membrane (17, 24). Login to comment 36 ABCC7 p.Val232Asp Since the folding defect in CFTR caused by the V232D mutation is correctable to wild-type levels, CF patients with this allele may benefit from treatment with folding correctors. Login to comment 37 ABCC7 p.Val232Asp The folding defect caused by the V232D mutation appears to be due to the introduction of a charged residue into a region of CFTR that is embedded in the lipid bilayer of the endoplasmic reticulum (ER) membrane (17, 24). Login to comment 38 ABCC7 p.Val232Asp Since the folding defect in CFTR caused by the V232D mutation is correctable to wild-type levels, CF patients with this allele may benefit from treatment with folding correctors. Login to comment 154 ABCC7 p.Val232Asp Yet, the mechanism by which the V232D mutation causes CF is not well documented and whether patients with this mutation can be treated with modulators of CFTR folding and channel activity is not clear. Login to comment 156 ABCC7 p.Val232Asp The V232D mutation is proposed to cause aberrant hydrogen bonding between TM4 and adjacent TM segments in CFTR (24). Login to comment 165 ABCC7 p.Val232Asp Thus, CF patients that harbor low frequency mutations, such as V232D, might be treated with small molecules that correct CFTR misfolding or potentiate CFTR channel activity. Login to comment 169 ABCC7 p.Val232Asp In doing so, Corr-4a may prevent the V232D mutation from causing the aberrant hydrogen bonding between TM segments in the bilayer proposed to cause premature degradation of CFTRV232D (24). Login to comment 191 ABCC7 p.Val232Asp Yet the mechanism by which the V232D mutation causes CF is not well documented, and whether patients with this mutation can be treated with modulators of CFTR folding and channel activity is not clear. Login to comment 193 ABCC7 p.Val232Asp The V232D mutation is proposed to cause aberrant hydrogen bonding between TM4 and adjacent TM segments in CFTR (24). Login to comment 202 ABCC7 p.Val232Asp Thus CF patients that harbor low-frequency mutations, such as V232D, might be treated with small molecules that correct CFTR misfolding or potentiate CFTR channel activity. Login to comment 206 ABCC7 p.Val232Asp In doing so, Corr-4a may prevent the V232D mutation from causing the aberrant hydrogen bonding between TM segments in the bilayer proposed to cause premature degradation of CFTRV232D (24). Login to comment